This application for continuation of the Breast Cancer Specialized Program of Research Excellence (SPORE) at Duke University proposes a highly interactive, multidisciplinary and inter-institutional program for a second period of funding. Four research projects and an ongoing developmental research project representing the translational components of five major research programs within the Duke Breast Cancer Research Program, four cores, a career development and a research development program are proposed to further our translational research in breast cancer. Project 2-1: Hypoxia and chemoresistance in Breast Cancer, Co-investigators- Mark Dewhirst, Larry Marks, and David Brizel. Project 2-2: T helper responses to HER2/neu in Breast Cancer Patients 2, Coinvestigators-H. Kim Lyerly, Mike Morse, and Tim Clay Project 2-3: Genetic Modifiers of BRCA1 and BRCA2, Co-investigators- Joellen Schildkraut and Ed Iversen. Project 2-4: Application of Pharmacogenomics to Treatment of Breast Cancer Co-investigators- O. Michael Colvin, Jeff Marks and William Petros. Current Developmental Research Project: Breast Cancer Gene Expression After Total Estrogen Ablation, Co-investigators- Jeff Marks, Joe Nevins and Matt Ellis. The cores support the research programs (Core A: Administration, H. Kim Lyerly; Core B: Tissue Bank, Rex Bentley; Core C: Biostatistics and Informatics, Steve George; and Core D: Molecular and Cell Technology, Jeff Marks. The Career Development Program chaired by O. Michael Colvin and Victoria Seewaldt, aids the development of new investigators and the Developmental Research Program, chaired by Donald McDonnell provides funding of innovative projects.